Evidence map›Paper›PMID 37079382›Full record

ArticleThe Journal of infectious diseases2023

Mycobacterium tuberculosis Gene Expression Associated With Fluoroquinolone Resistance and Efflux Pump Inhibition.

Yuri F van der Heijden, Fernanda Maruri, Amondrea Blackman, Robert Morrison, Yan Guo, Timothy R Sterling

Open access · greenAbstract read
In one paragraph

Article in The Journal of infectious diseases, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.8field-weighted citation impact, top 31% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. Macrolide resistance inFrontiers in cellular and infection microbiology · 2025
    Article
  3. Article
  4. Efflux pump effects on levofloxacin resistance inAntimicrobial agents and chemotherapy · 2024
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 2 countries.

Yuri F van der HeijdenDivision of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.ORCID 0000-0001-7631-9796
Fernanda MaruriDivision of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.ORCID 0000-0001-9533-8239
Amondrea BlackmanDivision of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Robert MorrisonPathogenesis and Immunity Section, Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Yan GuoDepartment of Internal Medicine, University of New Mexico, Albuquerque, New Mexico, USA.
Timothy R SterlingDivision of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Vanderbilt University · USNational Institutes of Health · USUniversity of New Mexico · US

Funding

Fluoroquinolone Resistance in M. TuberculosisR01AI063200 · NIAID · VANDERBILT UNIVERSITY · PI STERLING, TIMOTHY R · 2006 to 2010
$1.8M
Fluoroquinolone resistance in patients with multidrug-resistant tuberculosisK08AI106420 · NIAID · VANDERBILT UNIVERSITY MEDICAL CENTER · PI VAN DER HEIJDEN, YURI F. · 2014 to 2018
$848k
Fluoroquinolones and Efflux-Mediated Cross Resistance in HIV-related TBR56AI118361 · NIAID · VANDERBILT UNIVERSITY MEDICAL CENTER · PI SHERMAN, DAVID R, STERLING, TIMOTHY R · 2016 to 2016
$696k
NIAID NIH HHS K08 AI106420NIAID NIH HHS R01 AI063200NIAID NIH HHS R56 AI118361
6 · The paper itself

Abstract

backgroundWe evaluated the relationship between response to efflux pump inhibition in fluoroquinolone-resistant Mycobacterium tuberculosis (Mtb) isolates and differences in gene expression and expression quantitative trait loci (eQTL).

methodsWe determined ofloxacin minimum inhibitory concentration (MIC) for ofloxacin-resistant and -susceptible Mtb isolates without and with the efflux pump inhibitor verapamil. We performed RNA sequencing (RNA-seq), whole genome sequencing (WGS), and eQTL analysis, focusing on efflux pump, transport, and secretion-associated genes.

resultsOf 42 ofloxacin-resistant Mtb isolates, 27 had adequate WGS coverage and acceptable RNA-seq quality. Of these 27, 7 had >2-fold reduction in ofloxacin MIC with verapamil; 6 had 2-fold reduction, and 14 had <2-fold reduction. Five genes (including Rv0191) had significantly increased expression in the MIC fold change >2 compared to <2 groups. Among regulated genes, 31 eQTLs (without ofloxacin) and 35 eQTLs (with ofloxacin) had significant allele frequency differences between MIC fold change >2 and <2 groups. Of these, Rv1410c, Rv2459, and Rv3756c (without ofloxacin) and Rv0191 and Rv3756c (with ofloxacin) have previously been associated with antituberculosis drug resistance.

conclusionsIn this first reported eQTL analysis in Mtb, Rv0191 had increased gene expression and significance in eQTL analysis, making it a candidate for functional evaluation of efflux-mediated fluoroquinolone resistance in Mtb.

Indexed as

Mycobacterium tuberculosisAntitubercular AgentsDrug Resistance, BacterialFluoroquinolonesGene ExpressionMicrobial Sensitivity TestsOfloxacinVerapamilAntitubercular AgentsFluoroquinolonesOfloxacinVerapamilefflux pump inhibitionexpression quantitative trait locifluoroquinolone resistancegene expressionMtb

Identifiers

PMID37079382
PMCPMC10428193
OpenAlexW4366463721

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.